Nutmeg and the processed products thereof (such as nutmeg oil) are useful compounds having been used for, for example, gastrointestinal drugs, headache medicines, and spices since ancient times.
On the other hand, for the purpose of imparting refreshing feeling in use or after use, cool-feeling materials are frequently mixed in various products such as cosmetics, hair care products, toiletry products, bath additives and pharmaceuticals; and as such a cool-feeling material, menthol is widely used.
It is considered cooling sensation is imparted by menthol as a result of direct action of menthol on the sensory nerve ending present in the skin or the mucosal tissue, and the investigation of the mechanism of imparting cooling sensation has been advanced.
Of the sensory nerves of rat, the neuron generating the inward ionic current as a response to a weak cold stimulus has been found to exhibit a similar responsiveness to menthol (Non Patent Literature 1). On the basis of this finding, it has been revealed that the cooling sensation due to the stimulus of menthol is caused by an inward ionic current.
As a receptor exhibiting response to menthol and cold stimulus, CMR-1 (cold and menthol sensitive receptor) has been identified from trigeminal nerve neuron (Non Patent Literature 2). This receptor is referred to as TRPM8 (Non Patent Literature 3), and the receptor, which is an excitatory ion channel belonging to the TRP ion channel family, is considered to cause the foregoing ionic current.
These reports have revealed that menthol binds to TRPM8 present in the sensory nerve to generate an inward current, and consequently the cooling sensation due to menthol arises.